Should the dosage of controlled-release oxycodone in advanced cancer be modified on the basis of patient characteristics?

Charles, Bruce, Hardy, Janet, Anderson, Helen, Tapuni, Angela, George, Rani and Norris, Ross (2014) Should the dosage of controlled-release oxycodone in advanced cancer be modified on the basis of patient characteristics?. Supportive Care in Cancer, 22 2: 325-330. doi:10.1007/s00520-013-1973-6


Author Charles, Bruce
Hardy, Janet
Anderson, Helen
Tapuni, Angela
George, Rani
Norris, Ross
Title Should the dosage of controlled-release oxycodone in advanced cancer be modified on the basis of patient characteristics?
Journal name Supportive Care in Cancer   Check publisher's open access policy
ISSN 0941-4355
1433-7339
Publication date 2014-02
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s00520-013-1973-6
Volume 22
Issue 2
Start page 325
End page 330
Total pages 6
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2014
Language eng
Formatted abstract
Purpose: This study aimed to investigate whether the characteristics of patients with advanced cancer explain the variability in oxycodone clearance, with the potential for this information to determine maintenance dosing.

Methods: Patients (n = 36) with advanced cancer who were receiving delayed-release oxycodone (Oxycontin®) (mean dose, 31.4 mg; range, 5–120 mg) mostly twice daily (mean duration = 80 days; range, 5–651 days) provided venous blood samples (n = 139, median = 3 per patient) drawn from 0.25 to 23.4 h post-dose. Plasma was assayed for oxycodone (mean = 39.4 ng/mL; range, 1–256 ng/mL) by high-performance liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic modeling was performed using nonlinear mixed-effects modeling (NONMEM).

Results: A one-compartment model with first-order absorption and elimination best described the data. Typical population values and between-subject variability (coefficient of variation, percent) for oxycodone clearance and the oral absorption rate constant were 73 L/h (31.9 %) and 0.0735 h (133 %), respectively. The volume of distribution was estimated based on literature values for intravenous oxycodone in cancer patients. The inclusion of weight, sex, age, creatinine clearance, and serum albumin concentration did not significantly explain pharmacokinetic variability in clearance or absorption rate constant. The subject with the most elevated liver function test values also had the lowest clearance per kilogram.

Conclusions: Oxycodone clearance was similar to that reported previously for healthy adults. Despite reports that patient characteristics significantly affect oxycodone pharmacokinetics, our results do not support alteration of current prescribing practices for maintenance dosing of Oxycontin® in most patients with advanced cancer. The influence of marked liver dysfunction on oxycodone clearance requires further investigation.
Keyword Oxycodone
Pharmacokinetics
Advanced cancer
Patient characteristics
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 29 September 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Health Services Publications
Official 2014 Collection
School of Pharmacy Publications
 
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